PGE2 is known as one of the metabolites in an arachidonic acid cascade. The PGE2 exhibits various activities such as a pain inducing and increasing action, a pro- or anti-inflammatory action, an uterine contractile action, a digestive peristalsis promoting action, an awaking action, a suppressive effect on gastric acid secretion, a hypotensive action, a platelet aggregation inhibition action, a bone-resorption promoting action, an angiogenic action, and the like.
PGE2 receptors are divided into four subtypes, EP1, EP2, EP3 and EP4, which have a wide distribution in various tissues. The activation of the EP 1 receptor is believed to increase intracellular Ca2+. The EP3 receptor is one of the receptors having different routes for second-messenger systems. Further, the activation of the EP2 and EP4 receptors is believed to cause the activation of an adenylate cyclase, and thus increase the intracellular cAMP level. Especially, the EP4 receptor is considered to be associated with smooth muscle relaxation, pro- or anti-inflammatory reactions, lymphocyte differentiation, mesangial cell relaxation or proliferation, gastric or enteric mucus secretion, or the like.
The inhibitors of the PGE2 receptor, that is, the “PGE2 antagonists”, exhibit binding activities to the PGE2 receptors. That is, the PGE2 antagonists exhibit a PGE2-antagonistic or PGE2-inhibiting action. Therefore, the PGE2 antagonists are expected as pharmaceuticals to treat PGE2-mediated diseases. It is expected that these PGE2 antagonists can be used as therapeutic drugs to treat EP4 receptors-related diseases, such as renal diseases, inflammatory diseases, various pains, or the like, by acting on the EP4 receptors, in humans or animals.
As a compound having a PGE2 antagonistic action, there has been reported a compound represented by the following formula, and particularly, such a compound is useful as an EP4 receptor agonist (Patent Document 1).

(wherein particularly X represents —CO— or lower alkylene, R5 represents H or lower alkyl, and R2 represents lower alkyl or aryl which may be substituted. Refer to the following publication for the details.)
[Patent Document 1] Pamphlet of International Publication No. WO 2005/061475